1. Field of the Invention
This invention relates to steroidal derivatives of glycolipids, in which steroids are bridged via a medium length hydrocarbon chain, to 1-thio-D-mannopyranoses or 1-thio-L-fucopyanoses as the carbohydrates, that protect an immunocompromised host against opportunistic infection.
2. Brief Description of Disclosures in the Art
The search for new immunostimulator agents for augmenting host defenses to combat infection, cancer and congenital immunodeficiency disorders is an increasingly important area of pharmaceutical endeavor. For example, see Surgery, Vol. 92, No. 2, pp. 138-145 (1982); Infection, Vol. 12 (1984) No. 117/157; and ibid., 270/82.
Glycolipids are known in the pharmaceutical arts, e.g. M. M. Ponpipom et al., in "Liposomes Technology Vol. III, Targeted Drug Delivery and Biological Interactions", ed. by G. Gregoriadis, CRC Critical Reviews, Ch. 7, pp. 95-115.
Steroidal glycosidic compounds are known in the art as being useful immunological adjuvants. For example see, U.S. Pat. No. 4,259,324; U.S. Pat. No. 4,229,441; U.S. Pat. No. 4,189,471 (all three patents being assigned to Merck & Co., Inc.); Carbohydrate Res. 67, pp. 55-63 (1978) by J. C. Chabala and T. Y. Shen; J. Med. Chem. 23, p. 1184-1188 (1980) by M. M. Ponpipom et al.; and Can. J. Chem. 58, pp. 214-220 (1980) by M. M. Ponpipom et al.
Glycosides are also known in the art for exhibiting pharmacological effects. For example, see U.S. Pat. No. 4,228,274; Chem. Pharm. Bull. Jap., 12, 528-532 (1964); and Proc. Nat'l Acad. Sci. USA, Vol. 78, No. 12, pp. 7294-7298 (1981).
Another reference, J. Med. Chem., 15, pp. 1284-1287 (1972), describes synthesis of epimeric 20- and 22-azacholesterols as potential therapeutic mediators for hyperfunctioning adrenal glands.
However, the above disclosures do not specifically describe glycolipids bearing steroidal substituents for use as host resistance enhancing agents, i.e., immunostimulators.
There is a continuing need and demand for safer and more effective agents in enhancing resistance to opportunistic bacterial and fungal invading agents in immunocompromised hosts.